1. Field of the Invention
This invention comprises the use of non-toxic sparingly soluble calcium and phosphate compounds as additives, particularly to candies and confectioneries that cause the release of calcium and phosphate ions into the oral cavity gradually and persistently for an appropriate and therapeutically useful period. The released calcium phosphate ions can diffuse into partially demineralized tooth enamel or dentin, leading to remineralization and repair of the caries lesion. The released calcium phosphate ions can also diffuse into dental plaque to cause remineralization of teeth and to reduce or eradicate cariogenic challenge in plaque following sucrose or sugar intake. Thus, these formulations can produce effective anticaries actions without the use of fluoride. The released calcium phosphate ions can also cause precipitation of calcium phosphate minerals inside open dentinal tubules and on exposed dentine surfaces to desensitize hypersensitive teeth. These agents will have minimal adverse effects and require little effort on the part of the user.
2. Summary of the Related Art
Edibles, chewables and confections have the potential of being an effective vehicle for delivering therapeutic agents to teeth because they permit protracted contact of the agent to the teeth with minimal effort on the part of a patient. Despite the desirability of such items as a vehicle for delivering anticarious agents to teeth, no effective embodiments of anticarious confections or candies (with or without sugar) have been developed in the art.
The effectiveness of prior attempts at using potential anticarious agents in edibles for oral consumption, i.e., chewing gums, for example, was reviewed by Edgar and Geddes (1990, Br. Dent. J. 24: 173-176). For example, dicalcium phosphate dihydrate (DCPD; CaHO4.2H2O), was used at a dose of 7.5 wt % and assessed for its effects on the calcium (Ca) and phosphate (PO4) concentrations in saliva (Pickel and Bilotti, 1965, J. Alabama Med. Soc. 2: 286-287). A chewing gum containing 10 wt % DCPD was assessed for anticarious effects in two different clinical studies (Finn and Jamison, 1967, J. Amer. Dent. Assoc. 74: 987-995; Richardson et al., 1972, J. Canad. Dent. Assoc. 6: 213-218). The results from the Richardson study showed that, although sugar-DCPD gum produced a lower caries score than did the gum containing sugar alone, the cariogenicity of the sugar-DCPD gum was equivalent to that of sugar-free gum. The marginal degree of effectiveness of DCPD as an anticaries gum additive in this study was accepted in the art as demonstrating that DCPD was ineffective as an anticarious agent. As a result of this study, there has been little interest or activity in the art in using calcium phosphate-containing gums as anticarious agents.
The feasibility of using two new calcium phosphate additives in bubble gum has been evaluated for effectiveness in increasing salivary mineral saturation levels and/or enhancing salivation (Chow et al., 1994, J. Dent. Res.73: 26-32). In these in vivo studies, monocalcium phosphate monohydrate (MCPM; Ca(H2PO4)2.H2O) and an equimolar mixture of dicalcium phosphate anhydrous (DCPA; CaHPO4) and tetracalcium phosphate (TTCP; Ca4(PO4)2O) were used as chewing gum additives. These studies showed that both the MCPM and DCPA/TTCP gums increased the calcium and phosphate concentrations in saliva during a chewing period of 16 minutes. The extent of increase was much greater than those produced by gums containing DCPD. The degree of saturation with respect to tooth mineral was significantly increased by both experimental gums, with greater increase being produced by the DCPA/TTCP gum. U.S. Pat. Nos. 5,037,639; 5,268,167; 5,427,768; and 5,437,857; issued to Tung, disclose and claim the use of amorphous calcium phosphate (Ca3(PO4)2) and derivatives as chewing gum additives for tooth remineralization.
While some of the above additives have had efficacy under some conditions, shortcomings have been associated with each. The DCPA/TTCP mixture requires an extensive preparation process: TTCP must be prepared in a furnace at a high temperature (1500xc2x0 C.) and then blended with commercially-available DCPA after each calcium phosphate salt has been ground to the desired particle size. ACP compounds must be precipitated in aqueous systems, thereby having variable composition and relatively undefined particles size. Also, the stability of ACP in gum base or a gel and perhaps in a confection may be limited, and a stabilizer may be required to achieve the desired shelf life.
Other calcium-containing compounds have been studied for their effectiveness in remineralization of teeth in situ. U.S. Pat. No. 5,378,131 to Greenberg disclosed the use of calcium glycerophosphate as a chewing gum additive for dental health benefits. This patent also disclosed the use of several other calcium compounds, including calcium lactate and calcium gluconate, to achieve an anticaries effect when used as a chewing gum additive. However, chewing gums containing calcium compounds as additives can only raise calcium concentration levels in saliva. In fact, phosphate concentration levels would be expected to be decreased as a result of chewing calcium-containing gums, based on the showing that saliva phosphate levels decrease with increased salivation stimulated by gum chewing (Chow et al., ibid.). Thus, these calcium-containing chewing gums disclosed by Greenberg are cariostatic, rather than anticarious. Consequently, there is a need for vehicles that release phosphate ions into the oral cavity in conjunction with increased calcium ion concentration to provide an anticaries effect not found in edibles known in the prior art.
In contrast to the recognized likely desirability of chewing gum as a vehicle for delivery of anticarious agents, candies have not been generally recognized as a means for delivering calcium and phosphate ions into the oral environment. A major reason for this is that sugar, the major ingredient of candies, is the chief culprit of dental caries. With the advent of sugar-free candies (i.e., candies that do not contain significant amount of fermentable carbohydrates), however, candies can be an effective means of delivering therapeutic agents for dental caries.
This invention provides candies and confectioneries (both sugar based and sugarless) that are formulated to release calcium and phosphate ions into the mouth of a human patient.
The invention provides a calcium phosphate-containing composition comprising a candy or confectionery and further comprising a calcium phosphate salt. In preferred embodiments, the candy or confectionary is sugar-free, though sugar-based candy may provide the benefits of the invention. In a most preferred embodiment, the calcium phosphate salt is xcex1-tricalcium phosphate. In other preferred embodiments, the calcium phosphate salt is xcex2-tricalcium phosphate, monocalcium phosphate monobasic, dicalcium phosphate anhydrous, dicalcium phosphate dihydrate, octacalcium phosphate, tetracalcium phosphate, and mixtures and combinations thereof. Preferably, the calcium phosphate salt comprises from about 0.5 to about 10 percent of the candy formulation by weight (weight percent, or wt %). More preferably, the calcium phosphate salt comprises from about 1 to about 5 wt % of the candy formulation. In the sugar-free candies of the invention, the calcium phosphate salts are provided with a particle size of less than about 50 xcexcm, and more preferably having a particle size of from about 1 to about 20 xcexcm. Sparingly-soluble calcium phosphate salts are appropriate but are not required for this embodiment of the invention, due to the preferred composition of the candies and confectioneries of the invention as described in detail herein. Although sugar-free candies and confectioneries are preferred, calcium phosphate-containing embodiments of the candies and confectioneries of the invention prepared using sugar (e.g., sucrose) are within the scope of the invention. In such embodiments, it will be recognized that the cariostatic and remineralizing benefits of the calcium phosphate components of the inventive candies and confectioneries will outweigh the cariogenic propensity of sugar.
In a further aspect, the invention provides a calcium phosphate-containing candy or confectionery that comprises a calcium compound and a phosphate salt. In preferred embodiments, the candy or confectionery is sugar-free. In preferred embodiments, the calcium compound is a sparingly-soluble calcium salt of glycerophosphate, lactate, gluconate, or fumarate. In other preferred embodiments, the calcium compound is a soluble compound, and is preferably calcium acetate or calcium chloride. In these embodiments, the candy is formulated to slow the release of calcium ions from the soluble calcium compound so that calcium ions are released over a 5 to 15 minute period.
Preferably, the candies provided in this aspect of the invention are formulated to contain calcium compounds at from about 0.5 to 10 weight percent of the candy. More preferably, the calcium compounds comprise from about 1 to about 5 weight percent of these candies. Additionally, the calcium compounds provided in the candies of this aspect of the invention are provided having a particle size of less than 50 xcexcm, more preferably from about 1 to about 20 xcexcm.
The candies of this aspect of the invention are also formulated to contain a phosphate salt. Preferred phosphate salts include but are not limited to Na2HPO4, NaH2PO4, and Ca(H2PO4)2.H2O. Preferably, the candies in this aspect of the invention are formulated to contain phosphate salts at from about 0.5 to 10 weight percent. More preferably, the phosphate salts comprise from about 1 to about 5 weight percent of these candies. Additionally, the phosphate salts provided in the candies of this aspect of the invention are provided having a particle size of less than 50 xcexcm, more preferably from about 1 to about 20 xcexcm.
Although sugar-free candies and confectioneries are preferred, calcium phosphate-containing embodiments of the candies and confectioneries of the invention prepared using sugar (e.g., sucrose) are within the scope of this aspect of the invention.
The invention also provides methods for remineralizing teeth to reduce or eliminate dental caries and other dental disease. The methods of the invention are provided wherein a human patient simply ingests into the oral cavity the candies or confectioneries to release calcium and phosphate ions into the mouth and onto teeth. In a preferred embodiment, the candy or confectionery is used as a lozenge, from about one to about five minutes, more preferably from about three to about ten minutes, and most preferably from about five to about fifteen or twenty minutes, to effect the release of calcium and phosphate ions into the mouth and in contact with teeth.
A preferred use for the methods of this invention is for remineralizing a dental lesion in a human. Another preferred use for the methods of the invention is for remineralizing dental plaque in a human. Yet another preferred use for the methods of this invention is for reducing cariogenic challenge to human teeth. The methods of the invention are also preferably used for desensitizing hypersensitive human teeth, and for remineralizing open dentinal tubules and exposed dentine surfaces in human teeth.
Certain preferred embodiments of the candies and confectioneries as well as useful methods for using such embodiments for treating and remineralizing teeth, are described in greater detail in the following sections of this application.